Comparison of radiographic and MRI osteoarthritis definitions and their combination for prediction of tibial cartilage loss, knee symptoms and total knee replacement: a longitudinal study.

OBJECTIVE: To describe the value of radiographic- and magnetic resonance imaging (MRI)-defined tibiofemoral osteoarthritis (ROA and MRI-OA, respectively) and in combination for predicting tibial cartilage loss, knee pain and disability and total knee replacement (TKR) in a population-based cohort. DESIGN: A radiograph and 1.5T MRI of the right knee was performed. ROA and MRI-OA at baseline were defined according to the Osteoarthritis Research Society International atlas and a published Delphi exercise, respectively. Tibial cartilage volume was measured over 2.6 and 10.7 years. Knee pain and disability were assessed at baseline, 2.6, 5.1 and 10.7 years. Right-sided TKRs were assessed over 13.5 years. RESULTS: Of 574 participants (mean 62 years, 49% female), 8% had ROA alone, 15% had MRI-OA alone, 13% had both ROA and MRI-OA. Having ROA (vs. no ROA) and MRI-OA (vs. no MRI-OA) predicted greater tibial cartilage loss over 2.6 years (-75.9 and -86.4 mm3/year) and higher risk of TKR over 13.5 years (Risk Ratio [RR]: 15.0 and 10.9). Only MRI-OA predicted tibial cartilage loss over 10.7 years (-7.1 mm3/year) and only ROA predicted onset and progression of knee symptoms (RR: 1.32-1.88). In participants with both MRI-OA and ROA, tibial cartilage loss was the greatest (over 2.6 years: -116.1 mm3/year; over 10.7 years: -11.2 mm3/year), and the onset and progression of knee symptoms (RR: 1.75-2.89) and risk of TKR (RR: 50.9) were the highest. CONCLUSIONS: The Delphi definition of MRI-OA is not superior to ROA for predicting structural or symptomatic OA progression but, combining MRI-OA and ROA has much stronger predictive validity.

KARAOKE: Krill oil versus placebo in the treatment of knee osteoarthritis: protocol for a randomised controlled trial.

BACKGROUND: Knee osteoarthritis (OA) is a common and important cause of pain and disability, but interventions aimed at modifying structures visible on imaging have been disappointing. While OA affects the whole joint, synovitis and effusion have been recognised as having a role in the pathogenesis of OA. Krill oil reduces knee pain and systemic inflammation and could be used for targeting inflammatory mechanisms of OA. METHODS/DESIGN: We will recruit 260 patients with clinical knee OA, significant knee pain and effusion-synovitis present on MRI in five Australian cities (Hobart, Melbourne, Sydney, Adelaide and Perth). These patients will be randomly allocated to the two arms of the study, receiving 2 g/day krill oil or inert placebo daily for 6 months. MRI of the study knee will be performed at screening and after 6 months. Knee symptoms, function and MRI structural abnormalities will be assessed using validated methods. Safety data will be recorded. Primary outcomes are absolute change in knee pain (assessed by visual analog score) and change in size of knee effusion-synovitis over 24 weeks. Secondary outcomes include improvement in knee pain over 4, 8, 12, 16 and 20 weeks. The primary analyses will be intention-to-treat analyses of primary and secondary outcomes. Per protocol analyses adjusting for missing data and for treatment compliance will be performed as the secondary analyses. DISCUSSION: This study will provide high-quality evidence to assess whether krill oil 2 g/day reduces pain and effusion-synovitis size in older adults with clinical knee OA and knee effusion-synovitis. If krill oil is effective and confirmed to be safe, we will provide compelling evidence that krill oil improves pain and function, changes disease trajectory and slows disease progression in OA. Given the lack of approved therapies for slowing disease progression in OA, and moderate cost of krill oil, these findings will be readily translated into clinical practice. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12616000726459. Registered on 02 June 2016. Universal Trial Number (UTN) U1111-1181-7087.

Factors associated with prevalent and incident foot pain: data from the Tasmanian Older Adult Cohort Study.

OBJECTIVES: To describe factors associated with prevalent and incident foot pain in a population-based cohort of older adults (n = 1092). STUDY DESIGN: Longitudinal observational study. MAIN OUTCOME MEASURES: Prevalent foot pain, incident foot pain after 5 years. METHODS: Potential correlates included demographic factors, anthropometry, leg strength, metabolic factors, steps per day (using pedometer), pain at 6 other sites, and psychological wellbeing. Data were analysed using log binomial models. RESULTS: Participants were aged 50-80 years (mean 63 years), 49% male, mean body mass index (BMI) 27.8 ± 4.7 at baseline. The prevalence of foot pain at baseline was 38% and the incidence of new pain over 5 years was 20%. BMI, pain at other sites (neck, hands, knees, pain at three or more sites), and poorer psychological wellbeing were independently associated with baseline foot pain. Baseline BMI and pain in the neck, hands, and knees were independently associated with incident foot pain; but change in weight or BMI, total number of painful joints and psychological wellbeing were not. Self-reported diabetes and cigarette smoking were not associated with prevalent or incident foot pain. CONCLUSIONS: This study demonstrates that greater body weight and joint pain at multiple sites were consistently associated with prevalent foot pain and predict incident foot pain. Addressing excess body mass and taking a global approach to the treatment of pain may reduce the prevalence and incidence of foot pain in older adults.

Association of childhood adiposity measures with adulthood knee cartilage defects and bone marrow lesions: a 25-year cohort study.

OBJECTIVE: To describe the associations between childhood adiposity measures and adulthood knee cartilage defects and bone marrow lesions (BMLs) measured 25 years later. METHODS: 327 participants from the Australian Schools Health and Fitness Survey (ASHFS) of 1985 (aged 7-15 years) were followed up 25 years later (aged 31-41 years). Childhood measures (weight, height and skinfolds) were collected in 1985. Body mass index (BMI), overweight status and fat mass were calculated. Participants underwent 1.5 T knee magnetic resonance imaging (MRI) during 2008-2010, and cartilage defects and BMLs were scored from knee MRI scans. Log binomial regressions were used to examine the associations. RESULTS: Among 327 participants (47.1% females), 21 (6.4%) were overweight in childhood. Childhood adiposity measures were associated with the increased risk of adulthood patellar cartilage defects (Weight relative risk (RR) 1.05/kg, 95% confidence interval (CI) 1.01-1.09; BMI 1.10/kg/m2, 1.01-1.19; Overweight 2.22/yes, 1.21-4.08; fat mass 1.11/kg, 1.01-1.22), but not tibiofemoral cartilage defects. Childhood adiposity measures were not significantly associated with adulthood knee BMLs except for the association between childhood overweight status and adulthood patellar BMLs (RR 2.87/yes, 95% CI 1.10-7.53). These significant associations persisted after adjustment for corresponding adulthood adiposity measure. CONCLUSION: Childhood adiposity measures were associated with the increased risk of adulthood patellar cartilage defects and, to a lesser extent, BMLs, independent of adulthood adiposity measures. These results suggest that adiposity in childhood has long-term effects on patellar structural abnormalities in young adults.

Associations between MRI-detected early osteophytes and knee structure in older adults: a population-based cohort study.

OBJECTIVES: To describe prevalence of osteophytes (OPs) detected only by magnetic resonance imaging (MRI) but not by standard X-ray in older adults and to evaluate longitudinal associations with knee structural changes. METHODS: 837 participants were randomly selected from the local community and had MRI scans to assess knee OPs and other structures. OPs detected only by MRI but not by standard X-ray were defined as MRI-detected early OPs (MRI-OPs for short). OPs detected by both MRI and X-ray were defined as established-OPs. RESULTS: The prevalence of MRI-OPs was 50% while the prevalence of established-OPs was 10% and no-OPs was 40% at total tibiofemoral (TF) compartment at baseline. Compared with no-OPs, participants with MRI-OPs had greater risks of increased cartilage defects in all TF compartments (RR 1.37, 95%CI 1.07-1.74) and bone marrow lesions (BMLs) only in medial TF compartment (RR 1.49, 95%CI 1.06-2.11), after adjustment for age, sex, BMI, cartilage defects, BMLs and/or joint space narrowing; participants with established-OPs had greater cartilage volume loss at total (ß -2.02, 95%CI -3.86, -0.17) and lateral tibial sites (ß -5.63, 95%CI -9.93, -1.32), greater risks of increased cartilage defects in total (RR 1.66, 95%CI 1.15-2.40) and medial TF compartments (RR 1.49, 95%CI 1.20-1.69) and BMLs in all TF compartments (RR 1.88, 95%CI 1.22-2.89), after adjustment for covariates. CONCLUSION: MRI-OPs were associated with changes in knee structures, and the associations were similar but not as prominent as those for established-OPs. These suggest MRI-OPs may have a role to play in knee early-stage osteoarthritic progression.

Association between MRI-detected osteophytes and changes in knee structures and pain in older adults: a cohort study.

OBJECTIVE: To describe cross-sectional and longitudinal associations between magnetic resonance imaging (MRI)-detected osteophytes (OPs) and knee structural abnormalities and knee pain in older adults. METHOD: A prospective population-based cohort study of 895 participants aged 50-80 years (mean age 62 years, 50% female) was performed. T1-or T2-weighted fat suppressed MRI was used to assess knee OPs, cartilage volume, cartilage defects and bone marrow lesions (BMLs) at baseline and after 2.6 years. Radiographically-detected OPs were scored according to the Osteoarthritis Research Society International (OARSI) atlas. Knee pain was assessed using a self-administered questionnaire at baseline, 2.6 and 5 years later. RESULTS: 85% of participants had MRI-detected OPs at baseline, while 10% of participants had radiographically-detected OPs. Cross-sectionally, higher gardes of MRI-detected OPs in all compartments were significantly, independently and site-specifically associated with higher prevalences of cartilage defects and BMLs, lower cartilage volume and higher prevalence of knee pain. Longitudinally, higher gardes of baseline MRI-detected OPs site-specifically predicted greater risks of any increase in cartilage defects or BMLs, and loss of cartilage volume in medial and lateral tibiofemoral (LTF) and total compartments over 2.6 years in multivariable analyses. These significant associations were similar in those without radiographically-detected OPs. MTF and total OP scores were significantly associated with change in total knee pain over 2.6 and 5 years but these became non-significant after adjustment for cartilage defects and BMLs. CONCLUSION: MRI-detected knee OPs are common and appear to be clinically relevant to knee structural changes in older adults.

Cross-sectional and longitudinal associations between serum inflammatory cytokines and knee bone marrow lesions in patients with knee osteoarthritis.

OBJECTIVE: To describe cross-sectional and longitudinal associations between serum levels of interleukin (IL) - 6, IL-17A, IL-17F, IL-23 and knee bone marrow lesions (BMLs) in patients with knee osteoarthritis (OA). DESIGN: Patients (n = 192) with symptomatic knee OA (mean 63 years, range 50-79, female 53%) were assessed at baseline and after 24 months. At each time point, serum IL-6, IL-17A, IL-17F and IL-23 were measured using Bio-Plex® Multiplex Immunoassays with Luminex xMAP technology. Knee BMLs were scored using the modified whole organ MRI score (WORMS) from T2 weighted fat-suppressed fast spin echo magnetic resonance imaging (MRI). Multivariable linear regression and log binominal regression were used to determine the associations between cytokines and BMLs. RESULTS: Baseline IL-6 (quarters) were significantly associated with total knee BMLs (P < 0.01 for the trend) as well as associated with an increase in BML score (P = 0.05 for the trend), after adjustment for confounders. Baseline IL-17F and IL-23 (highest quarters vs others) was associated with an increase in BML score in females (P = 0.04 for IL-17F; P = 0.01 for IL-23), but not in males, in multivariable analyses. In contrast, IL-17A was not significantly associated with BMLs in either females or males. CONCLUSION: IL-6 is associated with increased knee BMLs in both females and males with OA. Serum IL-17F and IL-23 predicted increased knee BML scores in females only, suggesting that inflammation is involved in BML pathogenesis in knee OA, especially in women. TRAIL REGISTRATION: ClinicalTrials.gov identifier: NCT01176344; Australian New Zealand Clinical Trials Registry: ACTRN12610000495022.

Predictors of shoulder pain and shoulder disability after one year in diabetic outpatients.

OBJECTIVE: To investigate factors associated with changes in shoulder pain and disability in diabetic outpatients over 1 yr. METHODS: Cross-sectional study with 12-month follow-up in diabetic outpatients (n = 179) using the shoulder pain and disability index (SPADI) and SF-36 version 2. RESULTS: Patients with diabetes and shoulder pain or disability are more likely to be older and female. After 12 months of follow-up, one-quarter of participants without pre-existing symptoms at baseline developed clinically significant pain (28%) or disability (25%). Of the patients with pre-existing shoulder pain or disability, half reported clinically significant worsening (10 percentage points) in shoulder pain (58%) or disability (45%) over 12 months. Few patients demonstrated clinically significant improvement in pain (11%) or disability scores (19%). The remaining one-third of the patients reported no change in symptoms (30% pain; 35% disability). Increasing intensity of pain scores between baseline and 12 months was associated with older age, higher HbA(1c) and less pain at baseline. Increasing disability score between baseline and 12 months was associated with having had eye laser surgery, greater pain at baseline and less disability at baseline. CONCLUSION: Shoulder pain and disability are common, and persistent in adults with diabetes. Having higher HbA(1c) levels or having had treatment for retinopathy was associated with worsening shoulder pain and disability, confirming that glycaemic control and diabetic complications are associated with worsening shoulder pain or disability over 12 months of observation.

Osteoporosis screening in people with airways disease.

We tested associations between risk factors and bone mineral density in airways disease subjects, and developed a clinical screening tool to identify people who could benefit from bone mineral density testing. Subjects were recruited through hospital outpatients and pharmacies (Newcastle, n = 172). With survey refinement, we then tested a revised tool in a second sample (Adelaide, n = 317). Study factors included oral/inhaled corticosteroid use, asthma severity, respiratory admissions, physical activity, percent predicted forced expiratory volume in one second (FEV1), body mass index, and smoking history. Outcomes were bone mineral density of lumbar vertebra (L2-4) and total (or neck of) femur. Analysis was logistic regression with generation of a simple screening algorithm based upon coefficients. Scoring algorithm risk factors for T-score of < - 2.0: age > or = 68 = 10 points, bone mineral density < 20 = 25, weight < 60 kg = 20, 60-69 kg = 10, > or = 80 cigarette pack years = 15, low-level leisure activity = 5, area under receiver operator curve 0.83. For a cut-off score of 10, sensitivity was 91.2%, specificity 53.9%, positive and negative predictive values 52.3 and 91.7%, and 67.2% were correctly classified. In conclusions, our model has acceptable sensitivity, although limited specificity. Use of this tool may reduce unnecessary referrals for bone mineral density measurement.